The simultaneous study, conservation, and sustainable use of natural resources in tropical biodiversity hotspots require collaborative research partnerships of unprecedented scope and complexity, and the alarming rate at which biodiversity is being lost in many tropical regions has resulted in an urgent need for such efforts. We have assembled a multi-disciplinary, multi-institutional, international team to address the following objectives: 1) undertake surveys of biodiversity present in select taxonomic groups within the tropical forests of southeastern Sulawesi, a poorly studied yet threatened area of high species endemism within the biodiversity hotspot Wallacea; 2) explore the application of micro- and macro-organisms for natural product development for specific human health and bioenergy issues; 3) use the information from biodiversity surveys to develop recommendations for strategies to conserve endangered biomes and associated traditional and scientific knowledge bases; 4) develop and encourage local conservation planning, education, and outreach efforts that are ecologically, economically, and socio-politically sound; and 5) develop strong, equitable partnerships with effective international agreements relating to technology transfer, materials access, and benefit sharing. The project is organized into six Associate Programs: Macroorganism surveys; Microbial surveys; Discovery of energy solutions; Discovery of human health solutions; Conservation research and vertebrate surveys; and Conservation partnerships, training, and ethics. Our team includes scientists from three US Universities: UC Davis (lead), UC Berkeley, and UC San Francisco, and three prominent Indonesian institutions: Indonesian Institute of Science (lead agency), Indonesian Ministry of Forestry, and Bandung Institute of Technology. We will also form partnerships with private companies aimed at the commercial development of natural products for Pharmaceuticals and energy production, and we have secured collaborators from several other leading research institutions (e.g., Bishop Museum). An Indonesian-based Steering Committee, an International Advisory Board, and a web-based telecommunications and data-sharing network will provide critical guidance and interactive feedback loops for all participants throughout the course of the project. The results of this project will make significant contributions to a broad range of issues, including knowledge of patterns of biodiversity in southeast Asia, identification and isolation of natural products with potential therapeutic value to treat globally important diseases and to address human energy needs, development of effective biodiversity conservation strategies and proactive outreach and education programs to promote those strategies, and establishment of models for effective and equitable international collaborative partnerships and ethical and sustainable international sharing of biogenetic resources.